Trial Outcomes & Findings for Genes in Predicting Outcome of Patients With DLBCL Treated With Rituximab and Combination Chemotherapy (R-CHOP) (NCT NCT00450385)

Last Updated: 2017-06-23

Results Overview

The investigators aim to determine a list of genes and construct survival prediction model(s) that will predict the overall survival at 30 months in DLBCL patients prospectively treated with R-CHOP chemotherapy. Overall survival time will be calculated from the date of the diagnosis until death or last follow-up examination.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

30 months

Results posted on

2017-06-23

Participant Flow

A total of 60 patients were consented, however, only 57 of these patients were found to be eligible for enrollment per the protocol.

Participant milestones

Participant milestones
Measure	R-CHOP Patients will receive R-CHOP for 6 to 8 cycles: * Rituximab 375 mg/m2 on day 1 * Cyclophosphamide 750 mg/m2 IV on day 1 * Doxorubicin 50 mg/m2 on day 1 * Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 * Prednisone 100 mg orally days 1-5, repeated every 21 days.
Overall Study STARTED	57
Overall Study COMPLETED	44
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	R-CHOP Patients will receive R-CHOP for 6 to 8 cycles: * Rituximab 375 mg/m2 on day 1 * Cyclophosphamide 750 mg/m2 IV on day 1 * Doxorubicin 50 mg/m2 on day 1 * Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 * Prednisone 100 mg orally days 1-5, repeated every 21 days.
Overall Study Death	3
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	2
Overall Study Lack of Efficacy	2
Overall Study Adverse Event	1
Overall Study Physician Decision	1
Overall Study Other	3

Baseline Characteristics

Genes in Predicting Outcome of Patients With DLBCL Treated With Rituximab and Combination Chemotherapy (R-CHOP)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	R-CHOP n=57 Participants Patients will receive R-CHOP for 6 to 8 cycles: * Rituximab 375 mg/m2 on day 1 * Cyclophosphamide 750 mg/m2 IV on day 1 * Doxorubicin 50 mg/m2 on day 1 * Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 * Prednisone 100 mg orally days 1-5, repeated every 21 days.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants
Age, Categorical >=65 years	32 Participants n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Region of Enrollment United States	57 Participants n=5 Participants

PRIMARY outcome

Timeframe: 30 months

Population: The study required a minimum of 90 participants for gene expression analyses from which survival prediction model(s) could be derived. Due to actual participant accrual (57) being far below the minimum number of participants required, no data were collected on gene expression, and no survival prediction models were constructed.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 24 Months

Population: The study required a minimum of 90 participants for associated biomarker analyses. Due to actual participant accrual (57) being far below the minimum number of participants required, no biomarker data were collected.

The investigators aim to determine the usefulness of biomarkers associated with the antitumor effects of rituximab (e.g. immunoglobulin GFc receptor genotypes, CD20 protein expression and gene expression profiles) to predict overall survival of DLBCL patients treated with R-CHOP therapy and followed for at least 24 months or until death.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 2 Years

Population: The comparison could not be made because the study required a minimum of 90 participants for initial gene expression analyses from which survival prediction model(s) would be derived. Due to actual participant accrual (57) being far below the minimum number of participants required, no gene expression or survival prediction data were collected.

The investigators will compare the ability of constructed survival models to predict survival in DLBCL patients receiving R-CHOP therapy

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 Months

Population: The determination could not be made because the study required a minimum of 90 participants for biomarker analyses and derivation of survival prediction model(s). Due to actual participant accrual (57) being far below the minimum required, no data were collected on the ability of models and/or biomarkers to predict time to treatment failure.

The investigators aim to determine the ability of the models and/or biomarkers associated with the anti-tumor effects of rituximab to predict 24-month time to treatment failure, defined as disease progression, death or initiation of new treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 8 cycles, about 24 weeks

Rate of participants achieving complete response (CR), complete response/unconfirmed (CRu) partial response (PR) according to Non-Hodgkin's Lymphoma response criteria.

Outcome measures

Outcome measures
Measure	R-CHOP n=57 Participants Patients will receive R-CHOP for 6 to 8 cycles: * Rituximab 375 mg/m2 on day 1 * Cyclophosphamide 750 mg/m2 IV on day 1 * Doxorubicin 50 mg/m2 on day 1 * Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 * Prednisone 100 mg orally days 1-5, repeated every 21 days.
Overall Response Rate of Study Participants at the End of Protocol Therapy Complete Response (CR)	40 Participants
Overall Response Rate of Study Participants at the End of Protocol Therapy Complete Response unconfirmed (CRu)	0 Participants
Overall Response Rate of Study Participants at the End of Protocol Therapy Partial Response (PR)	7 Participants
Overall Response Rate of Study Participants at the End of Protocol Therapy Progressive Disease (PD)	2 Participants
Overall Response Rate of Study Participants at the End of Protocol Therapy Unknown	8 Participants

SECONDARY outcome

Timeframe: Baseline

Number of participants from whom paraffin-embedded DLBCL tissue samples were collected for future studies.

Outcome measures

Outcome measures
Measure	R-CHOP n=57 Participants Patients will receive R-CHOP for 6 to 8 cycles: * Rituximab 375 mg/m2 on day 1 * Cyclophosphamide 750 mg/m2 IV on day 1 * Doxorubicin 50 mg/m2 on day 1 * Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 * Prednisone 100 mg orally days 1-5, repeated every 21 days.
Number of Participants From Whom Fixed Tissue Samples Were Collected for Future Studies.	57 Participants

Adverse Events

R-CHOP

Serious events: 4 serious events

Other events: 3 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	R-CHOP n=57 participants at risk Patients will receive R-CHOP for 6 to 8 cycles: * Rituximab 375 mg/m2 on day 1 * Cyclophosphamide 750 mg/m2 IV on day 1 * Doxorubicin 50 mg/m2 on day 1 * Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 * Prednisone 100 mg orally days 1-5, repeated every 21 days.
Gastrointestinal disorders Abdominal pain	3.5% 2/57 • Number of events 2
Gastrointestinal disorders Diarrhea	1.8% 1/57 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	3.5% 2/57 • Number of events 2
Blood and lymphatic system disorders Febrile neutropenia	1.8% 1/57 • Number of events 1
General disorders Fever	1.8% 1/57 • Number of events 1
Infections and infestations Infection - Other	1.8% 1/57 • Number of events 1
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy)	1.8% 1/57 • Number of events 1
Renal and urinary disorders Urinary frequency	1.8% 1/57 • Number of events 1

Other adverse events

Other adverse events
Measure	R-CHOP n=57 participants at risk Patients will receive R-CHOP for 6 to 8 cycles: * Rituximab 375 mg/m2 on day 1 * Cyclophosphamide 750 mg/m2 IV on day 1 * Doxorubicin 50 mg/m2 on day 1 * Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 * Prednisone 100 mg orally days 1-5, repeated every 21 days.
Skin and subcutaneous tissue disorders Alopecia	1.8% 1/57 • Number of events 1
Gastrointestinal disorders Anorexia	1.8% 1/57 • Number of events 1
Metabolism and nutrition disorders Cholesterol, serum-high (hypercholestremia)	1.8% 1/57 • Number of events 1
Gastrointestinal disorders Constipation	3.5% 2/57 • Number of events 4
General disorders Constitutional Symptoms - Other	1.8% 1/57 • Number of events 1
Nervous system disorders Dizziness	1.8% 1/57 • Number of events 2
Blood and lymphatic system disorders Edema: limb	1.8% 1/57 • Number of events 1
Nervous system disorders Extrapyramidal disorder	1.8% 1/57 • Number of events 1
General disorders Fatigue	3.5% 2/57 • Number of events 2
Blood and lymphatic system disorders Febrile neutropenia	1.8% 1/57 • Number of events 1
Gastrointestinal disorders Gastritis	1.8% 1/57 • Number of events 1
Nervous system disorders Headache	3.5% 2/57 • Number of events 2
Vascular disorders Hypertension	1.8% 1/57 • Number of events 1
General disorders Injection site reaction	1.8% 1/57 • Number of events 1
Psychiatric disorders Insomnia	1.8% 1/57 • Number of events 1
Blood and lymphatic system disorders Leukocytes (total WBC)	3.5% 2/57 • Number of events 3
Nervous system disorders Mood alteration	1.8% 1/57 • Number of events 1
Musculoskeletal and connective tissue disorders Myalgia	1.8% 1/57 • Number of events 1
Gastrointestinal disorders Nausea	1.8% 1/57 • Number of events 1
General disorders Pain	1.8% 1/57 • Number of events 2
Blood and lymphatic system disorders Platelet count decreased	3.5% 2/57 • Number of events 3
Skin and subcutaneous tissue disorders Rash/desquamation	1.8% 1/57 • Number of events 1
General disorders Sweating (diaphoresis)	1.8% 1/57 • Number of events 2
Gastrointestinal disorders Taste alteration (dysgeusia)	1.8% 1/57 • Number of events 1
Metabolism and nutrition disorders Uric acid, serum-high (hyperuricemia)	1.8% 1/57 • Number of events 1

Additional Information

Izidore Lossos MD

University of Miami

Phone: 305-243-4785

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place